The broad objective is to understand the relationship between cellular metabolism and a) membrane ionic permeabilities, b) transmembrane ionic gradients and c) subcellular compartmentation of various ions. Mitochondrial cation transport will be stressed, particularly Ca2 ion and the distribution of metabolites between mitochondrial and cytoplasmic compartments. The possible interplay between mitochondrial Ca2 ion and Na ion transport will be studied to determine whether the translocation of Na ion may regulate the levels of Ca2 ion within the cytosol. The experimental approach will involve comparative studies of isolated cells and mitochondria to detail regulatory influences. Intact cell studies will involve alteration of intracellular ion levels together with specific alterations in the permeability of membranes with monovalent and divalent cation specific "ionophores". The influence of certain hormones upon membrane permeability and metabolism will form part of the above studies. The studies outlined will be applied to isolated liver cells in comparison to a selected variety of tumor cells to determine the extent to which the indicated ions and their translocation between compartments affect the oxidative and glycolytic metabolism of tumor cells, as well as relevant hormonal influences.